Organic Reactions

How to Climb a Mountain, One Organic Reaction at a Time

O-chem is full of stick figure structures and loopy reaction mechanisms. But to understand their thermodynamics and kinetics, you’ll have to climb a mountain first.

Mountaineering isn’t for everyone. It’s a tough sport requiring physical strength, mental endurance, and a considerable amount of skill—not unlike organic chemistry. Most of the time, o-chem focuses on the details: which atoms in a molecule are most reactive, how they interact with other structures, etc. But organic reactions obey the same laws and principles of thermodynamics and kinetics as every other reaction in the universe, so it’s worth taking a minute to zoom out and take in the entire vista.

Drawing a map: energy peaks and valleys

Good mountain climbing expeditions typically start with a map that shows how far you’ll be going, the path you’ll take, and how high you’ll have to climb. Without this information, you won’t know how much food or water to pack or how long you’ll be gone. Thermodynamics gives us this information for chemical reactions.

How do you map these reactions? The energy of a reaction is described by the Gibbs Free Energy, where ΔG=ΔH-TΔS. ΔG is the overall change in energy, while ΔH is the change in enthalpy, T is the temperature, and ΔS is the change in entropy. Most of the time, the Gibbs Free Energy is determined by the change in enthalpy, H, which is the amount of energy it takes to break or form each bond. Weak bonds are unstable, easily broken, and high on the energy scale. Strong bonds are stable and difficult to break. They are low on the energy scale.

If the overall change in energy is negative – weak bond to strong bond – the reaction will slope downhill like the diagram on the left. This is like a ski slope. Once you’re at the top, you can coast all the way down. If the change in energy is positive – strong bond to weak bond – you’re stuck climbing the mountain on your own with no help from gravity (see the diagram on the right).

How much energy, exactly will the reaction produce or consume? You can measure it by doing experiments like calorimetry or by calculating the change in enthalpy and entropy if you know the structures of reactants and products (learn more about that in this lecture). These calculations are crucial if you want to make sure you have enough energy to get to your destination!

You did pack rock climbing gear, right?

Even spontaneous, exothermic reactions don’t always take place immediately or quickly under normal circumstances. That initial “hump” in the reaction diagram is called the “activation energy,” and it’s not always easy to overcome. Many reactions that are thermodynamically favorable, including combustion, don’t take place without a spark of some kind to ignite them. That spark provides the energy needed to start the reaction. If that energy barrier is large enough, it can make some reactions that are energetically very favorable take place very slowly or not at all under normal conditions.

There are a few things that can lower the activation energy. You can stabilize the intermediate state using an enzyme or catalyst, for example, lowering the energy of the transition state. But in real life, asking the mayor of your town to scrape off the top of a mountain to make it easier for you to climb isn’t likely to happen. Similarly, catalysts and enzymes tend to be hard to find and very specific to individual reactions.

Activation energies (Ea) without and with a catalyst

Some intermediates are more stable than others. If the intermediate is positively charged, like the carbocations in elimination reactions where a substituent is lost in the first step, groups that donate electrons can stabilize the intermediate and lower its energy. If the transition state is negatively charged, electron withdrawing groups can do the same thing.

Pace yourself

If thermodynamics acts as your map through the reaction, kinetics is your guide to pacing your climb. If two reactants are interacting to form a product, they need to have enough energy when they meet to overcome the activation barrier. Hikers carry energy-dense food to give them enough fuel to complete their climb, but reactants gain energy when they increase in temperature. The hotter a molecule gets, the faster it will move, cause it to collide more frequently with other atoms and molecules. This raises the chances of a successful reaction.

Increasing the number of compounds (concentration) can also increase the probability of a reaction. Of course, it also helps if the activation energy is low in the first place, so there isn’t as much of a barrier to overcome.

Speed and energy, described by kinetics and thermodynamics, are both important parameters in organic reactions. But with the proper gear and a little wisdom from those who have been there before, you too can experience the highs and lows of organic reactions.